The aims of the proposed research using chronic carbon monoxide exposure and the rat model are two-fold; 1) to detemine how and to what extent the myocardium is altered by work overloading occurring during prenatal and early postnatal development and, 2) to answer the question whether the changes which occur during this period result in irreversible alterations in cardiac morphology, composition and/or physiology in the adult long after the initial work overload is relieved. Studies in my laboratory and by others show that cardiomegaly is more dramatic in the young than the old. This may occur in CO for two reasons: 1) in addition to carboxyhemoglobin formation stimulating cardiac output, hemoglobin concentration is low and paradoxically decreases still further in young CO-exposed rats, further increasing cardiac volume flow work and, 2) both heart muscle cell hyperplasia and hypertrophy contribute to compensatory heart enlargement, whereas only the latter process does so in adults. I have evidence suggesting that irreversible changes in heart mass and composition result from severe CO-induced cardiomegaly in adults. Would such permanent lesions be equal or greater if induced during early heart development? CO exposure is ideally suited to this task, especially in utero. To test this hypothesis and to characterize cardiomegaly in pre- and early postnatal development, pregnant rats will be exposed to CO from the seventh gestational day onward. Newborn from these mothers will be sacrificed during 4 more weeks of exposure and during 4 seeks after termination of exposure. Other exposed males will be allowed to reach 100 days of age. The parameters to be measured include: standard hematology, cardiac morphometry, water content, DNA, RNA, protein hydroxyproline, lactate dehydrogenase activity and isozymes and cardiac muscle performance and pump function using an in situ open chest preparation. Such a study will provide insight into whether early relief of congenital heart defects associated with cardiomegaly results in complete or partial return to normal heart dimensions, composition and function.